Work will continue on the structure and activity of diphtheria toxin and its enzymicly active fragment, Fragment A. The sequence of the toxin will be extended beyond the C-terminus of Fragment A, and studies will be undertaken to measure the binding of anti-Fragment A antibodies and NAD, to whole toxin. Studies are continuing to study entry of toxin into cells and to perfect a means of measuring the intracellular ADP-ribosylation of EF-2. We are also attemtping to synthesize a toxin with altered (or hybrid) specificity by chemically cross-linking Fragment A to selected receptor-binding portions of other toxins, or to antibodies against cell-surface antigen. Structure-activity studies on Ps. aeruginosa exotoxin, and cholera toxoid are also underway. BIBLIOGRAPHIC REFERENCES: Collier, R.J. (1975) Diphtheria toxin: mode of action and structure. Bacteriol. Rev. 39, 54-85. DeLange, R.J., Drazin, R., and Collier, R.J. (1976) Amino acid sequence of fragment A, and enzymically active fragment from diphtheria toxin. Proc. Nat. Acad. Sci. USA 73, 69-72.